Cellular Immune Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition with unknown aetiology, Myalgic encephalomyelitis unclear pathophysiology and with no diagnostic test or biomarker available. Many patients report their ME/CFS began after an acute infection, and subsequent increased frequency of infections, such as colds or influenza, is common. These factors imply an altered immunological status exists in ME/CFS, in at least a proportion of patients, yet previous studies of peripheral immunity have been discrepant and inconclusive. The UK ME/CFS Biobank, which has collected blood samples from nearly 300 clinically-confirmed ME/CFS patients, enables large-scale studies of immunological function in phenotypically well-characterised participants. In this study, herpes virus serological status and T cell, B cell, NK cell and monocyte populations were investigated in 251 ME/CFS patients, including 54 who were severely affected, and compared with those from 107 healthy participants and with 46 patients with Multiple Sclerosis. There were no differences in seroprevalence for six human herpes viruses between ME/CFS and healthy controls, although seroprevalence for the Epstein-Barr virus was higher in multiple sclerosis patients. Contrary to previous reports, no significant differences were observed in NK cell numbers, subtype proportions or in vitro responsiveness between ME/CFS patients and healthy control participants. In contrast, the T cell compartment was altered in ME/CFS, with increased proportions of effector memory CD8 + T cells and decreased proportions of terminally differentiated effector CD8 + T cells. Conversely, there was a significantly increased proportion of mucosal associated invariant T cells (MAIT) cells, especially in severely affected ME/CFS patients. These abnormalities demonstrate that an altered immunological state does exist in ME/CFS, particularly in severely affected people. This may simply reflect ongoing or recent infection, or may indicate future increased susceptibility to infection. Longitudinal studies of ME/CFS patients are needed to help to determine cause and effect and thus any potential benefits of immuno-modulatory treatments for ME/CFS.

Perturbation of effector and regulatory T cell subsets in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

“…Thus, it is interesting to note that we observed differences in CD8+ but not in DN MAIT cells in ME/CFS subjects, suggesting that these are different lineages or subsets. Taken together, it is conceivable that a disruption in the microbiome results in chronic activation of MAIT cells and an exhausted state in ME/CFS patients, which is similar to what has been seen with the Th17 subset (Cliff et al, 2019).…”

“…MAIT cells selectively respond to a broad range of bacteria that possess the biosynthetic pathway for riboflavin metabolism (Gold et al, 2010;Le Bourhis et al, 2010;Kjer-Nielsen et al, 2012;Meierovics et al, 2013). A recent study found significant changes in the frequency of CD8+ MAIT cells in Multiple Sclerosis and severe ME/CFS patients (Cliff et al, 2019). We did not observe significant changes in the frequency of MAIT cells as a percentage of PBMC or T cells, which could be due to fact that this T cell subset is highly variable and has up to a 40-fold difference in range, even among healthy humans (Ben Youssef et al, 2018), and that most of our patient group was not characterized as severe.…”

Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations

“…Cytokines reported to be altered in abundance include TNF-α, TGF-β, IFN-γ, IL-1α, IL-1β, IL-6, and IL-4 (1,(5)(6)(7)(8)(9)(10). Some studies have also reported differences in the frequency of CD4 + versus CD8 + T cells, Tregs, and/or memory T cells in patients with ME/CFS (10)(11)(12)(13)(14)(15)(16).…”

Comprehensive Circulatory Metabolomics in ME/CFS Reveals Disrupted Metabolism of Acyl Lipids and Steroids

“…At least half of the 11 major organ systems in the human body appear to be disrupted in ME/CFS patients. Some established instances include the reported dysfunction of several types of immune cells [2][3][4][5], as well as elevated levels of inflammatory cytokines plasma levels in patients compared to healthy controls [6,7]. Neuroimaging has detected a number of abnormalities [8][9][10], and impaired cognitive function is a predominant feature of the disease.…”